Featured Research

from universities, journals, and other organizations

Improving safety, effectiveness of lithium therapy: Closer than ever

Date:

March 11, 2014

Source:

University of South Florida (USF Health)

Summary:

Lithium, one of the oldest and most widely used drugs to treat neuropsychiatric illnesses, such as bipolar disorder, has a serious drawback -- toxicity. In a continued effort to find a safer form of lithium, researchers have discovered that lithium salicylate, an alternative salt form, might be the answer.

Lithium, one of the oldest and most widely used drugs to treat neuropsychiatric illnesses, such as bipolar disorder, has a serious drawback -- toxicity. In a continued effort to find a safer form of lithium, researchers at the University of South Florida (USF) have discovered that lithium salicylate, an alternative salt form, might be the answer.

Related Articles

The researchers found that oral lithium salicylate produced steady lithium levels up to 48 hours in rats without the toxic spike associated with the rapid absorption of current FDA-approved lithium carbonate. They concluded that lithium salicylate could be more effective than lithium carbonate, yet without accompanying risks of toxicity, a potentially important development in the next generation of lithium therapeutics.

Their study results appeared in a recent issue of RSC Advances, the journal of the Royal Society of Chemistry.

While lithium carbonate has been very effective for the treatment of mania in bipolar disorder, and credited for reducing suicides in depressive phases of the disease, patients who take lithium carbonate are often noncompliant because of adverse effects, including hand tremor, diarrhea, vomiting, weight gain and decreased thyroid function. New drugs that are as effective as lithium carbonate, but without toxicity, have not been forthcoming.

"Despite its narrow therapeutic window and the emergence of proprietary alternatives, U.S. FDA-approved lithium therapeutics are still regarded as the 'gold standard' for the treatment of the manic phase of bipolar disorder," said study lead author Adam J. Smith, PhD, a neuroscientist at the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery, at USF Health.

Crystal engineering is the design and synthesis of molecular solid crystal structures with desired properties using intermolecular interactions, Smith said.

For their latest study published in RSC Advances, the researchers tested two previously untested salts of lithium -- salicylate and lactate -- both of which are structurally different from lithium carbonate. In laboratory rats, they found that lithium salicylate and lithium lactate exhibited "profoundly different pharmacokinetics" when compared to the FDA-approved and widely used lithium carbonate. Pharmacokinetics is the way the body absorbs, distributes and gets rid of a drug.

"To our knowledge, this is the first pharmacokinetic study of lithium salicylate and lithium lactate in laboratory animals," Smith said.

The findings support earlier suggestions that an ideal lithium preparation would be one that would both "flatten" high blood level peaks and also slow declining blood concentrations, the researchers report.

"This is exactly the pharmacokinetic profile produced by lithium salicylate in our study," said senior author Doug Shytle, PhD, also of the Center of Excellence for Aging and Brain Repair at USF Health. "Remarkably, lithium salicylate produced elevated levels of lithium in the blood and brain 48 hours after the dose, but without the sharp peaks that contribute to the toxicity problems of lithium in the currently used form."

That 48-hour window, the researchers said, represents a critical difference between lithium salicylate and current FDA-approved lithium therapeutics. If these preclinical results hold true in humans, this would allow for a less frequent dosing regimen and possibly fewer troublesome side effects that plague conventional lithium therapy.

"Psychiatry has long struggled with the fact that, while lithium is highly effective for treating bipolar disorder, the narrow therapeutic window and side effect profile often makes lithium both difficult and sometimes dangerous to work with clinically," said Todd Gould, MD, of the Department of Psychiatry at the University of Maryland, an expert in the mechanisms of lithium and the neurobiology of bipolar disorder.

"The pharmacokinetic data by Dr. Smith and colleagues suggests that lithium salts other than the commonly used lithium carbonate may have a broader therapeutic window and potentially fewer side effects. Studies in humans will be needed to confirm safety and demonstrate that the pharmacokinetic profile observed in rats is similarly observed in humans."

USF researchers continue to pursue a safer, more effective lithium therapy, and expect to soon conduct the experiments required to support early clinical trials.

University of South Florida (USF Health). (2014, March 11). Improving safety, effectiveness of lithium therapy: Closer than ever. ScienceDaily. Retrieved March 31, 2015 from www.sciencedaily.com/releases/2014/03/140311124317.htm

Featured Research

Mar. 31, 2015  Researchers have illuminated an important distinction between mice and humans: how human livers heal. The difference centers on a protein called PPAR alpha which activates liver ... full story

Mar. 31, 2015  Researchers have recorded the first direct observations of the micro-scale mechanisms behind the ability of skin to resist tearing. The results could be applied to the improvement of artificial skin, ... full story

Mar. 31, 2015  Fewer than half of the physicians trained in the United States in 2013 received formal education or training on the subject of exercise, according to new research. "There are immense medical benefits ... full story

Mar. 31, 2015  Memory and as well as connections between brain cells were restored in mice with a model of Alzheimer's given an experimental cancer drug, researchers report. "With this treatment, cells under ... full story

Mar. 31, 2015  Increasing state alcohol taxes could prevent thousands of deaths a year from car crashes, say researchers, who found alcohol-related motor vehicle crashes decreased after taxes on beer, wine and ... full story

Mar. 31, 2015  Alcoholism takes a toll on every aspect of a person's life, including skin problems. Now, a new research report helps explain why this happens and what might be done to address it. "The clinical ... full story

Mar. 31, 2015  A new population of 'memory' immune cells has been discovered by scientists, throwing light on what the body does when it sees a microbe for the second time. This insight, and others like it, will ... full story

Mar. 31, 2015  Coronary heart disease and stroke, two of the leading causes of death in the United States, are diseases associated with heightened platelet reactivity. A new study in humans suggests an underlying ... full story

Mar. 31, 2015  A new study had researchers seeking answers to why the therapeutic benefit afforded by SSRIs was so limited in children and teenagers. If researchers can uncover the biological mechanisms preventing ... full story

Featured Videos

Solitair Device Aims to Takes Guesswork out of Sun Safety

Reuters - Innovations Video Online (Mar. 31, 2015)  The Solitair device aims to take the confusion out of how much sunlight we should expose our skin to. Small enough to be worn as a tie or hair clip, it monitors the user&apos;s sun exposure by taking into account their skin pigment, location and schedule. Matthew Stock reports.
Video provided by Reuters

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015)  Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline.
Video provided by Washington Post

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015)  Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17
Video provided by AFP

June 24, 2011  Lithium profoundly prevents the aggregation of toxic proteins and cell loss associated with Parkinson's disease (PD) in a mouse model of the condition. Preclinical research is aimed at ... full story

June 17, 2010  Lithium has been established for more than 50 years as one of the most effective treatments for manic depression, clinically termed bipolar disorder. However, scientists have never been entirely sure ... full story

June 7, 2010  Lithium is the most effective treatment for bipolar disorder. However, its use is limited because of neurological side effects and a risk for overdose-induced toxicity. Researchers have now ... full story

May 21, 2010  Though it has been prescribed for over 50 years to treat bipolar disorder, there are still many questions regarding exactly how lithium works. Researchers have provided solid evidence that lithium ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.